A critical reinforcing effect of cigarette smoking is believed to be acute relief of negative affect (anxiety, sadness, irritability, etc.). Smoking clearly relieves negative affect caused by smoking abstinence (i.e. withdrawal), and negative affect after quitting smoking increases the risk of relapse. However, it is not clear that smoking acutely relieves negative affect from "sources" other than abstinence, such as environmental stressors, which smokers commonly experience in the natural environment. Due to limitations inherent in clinical research, this question may best be addressed with well-controlled laboratory research. What is needed is a lab study that includes more than one source of negative affect so that results across different sources can be compared within the same subject sample, using the same measures of negative affect, and under the same experimental procedures. This is the important and novel objective of the current proposal: to examine the degree to which the relationship between negative affect and smoking depends on the source of that negative affect. We will employ four different procedures to briefly induce negative mood. Demands of these procedures vary in key ways (e.g. active coping vs. no active coping) and will help us determine the conditions under which smoking is associated with negative affect. In addition, the 200 smoking subjects will be randomly assigned to one of three groups that differ in smoking and/or nicotine exposure (i.e. between-subjects factor), those who: smoke a nicotine cigarette, smoke a denicotinized cigarette, or do not smoke at all. Comparisons among these groups will determine whether nicotine per se or smoking behavior alone, without nicotine (suggesting conditioned effects), is responsible for the associations between smoking and negative affect. Affect will be assessed via multiple response domains: self-report, psycho physiological, and behavioral. Primary specific aims are to examine: 1) whether acute tobacco smoking relieves negative affect as a function of source, 2) whether negative mood induction increases smoking behavior as a function of source, and 3) the association between negative affect relief and subsequent smoking behavior. In a secondary aim, we will: 4) explore individual differences in these effects. If smoking relieves negative affect from all four sources, this will strengthen the commonly held, but rarely demonstrated, notion that smoking does in fact acutely relieve negative affect, under virtually all conditions. However, if smoking relieves negative affect selectively, this finding will suggest that smoking's ability to relieve negative affect is limited to only certain conditions. Finally, if results for affect relief versus smoking behavior are inconsistent (i.e., aim #3), the traditional negative reinforcement explanation for the increase in smoking during negative mood will need to be reconsidered, warranting other explanations. In sum, this research will help address the fundamental question of why cigarette smoking is reinforcing. [unreadable] [unreadable]